Passive diffusion active/carrier-mediated transport

Figure 1 General pathways through which molecules can actively or passively cross a monolayer of cells. (A) Endocytosis of solutes and fusion of the membrane vesicle with the opposite plasma membrane in an active process called transcytosis. (B) Similar to A, but the solute associates with the membrane via specific (e.g., receptor) or nonspecific (e.g., charge) interactions. (C) Passive diffusion between the cells through the paracellular space. (C, C") Passive diffusion (C ) through the cell membranes and cytoplasm or (C") via partitioning into and lateral diffusion within the cell membrane. (D) Active or carrier-mediated transport of an otherwise poorly membrane permeable solute into and/or out of a cellular barrier.

Carrier-mediated transport, Active Efflux, Passive (trans and para cellular) diffusion... 

Tetracyclines bind to the 305 ribosomal subunit and interfere with bacterial protein synthesis. They are bacteriostatic at normal therapeutic concentrations, but bactericidal at high concentrations. They enter bacteria by passive diffusion and an active carrier-mediated process. Mammalian cells do not possess the tetracycline transport mechanism. The tetracyclines are most active at acidic pH, which is of benefit in the treatment of abscesses. 

Figure 2 Schematic illustration of the (transport) properties of the blood-brain barrier. Shown is the influence of astrocyte endfeet at the brain capillary endothelial cell. This cell has narrow tight junctions, low pinocytotic activity, many mitochondria, and luminal anionic sites that hinder the transport of negatively charged compounds. Passive hydrophilic transport occurs via paracellular diffusion (tight junctions), whereas passive lipophilic transport is a transcytotic process. Adsorptive-, receptor-, and carrier-mediated transport has been indicated. The metabolic properties of the BBB are illustrated by the various enzymes at the BBB [from (157), with permission].

Analytes that are derived from the blood plasma can be conveniently divided into those that are actively transported and typically maintained at homeostatic levels, as opposed to those that diffuse down concentration gradients. In between is carrier-mediated transport, which is rate limited typically by a saturable enzymatic transporter system. The passive diffusion of macromolecules such as proteins is influenced by the molecular sieving effect of various barriers that are constituted by basement membranes with varying degrees of effective pore size . 

The properties of the carriers involved in both active and passive transport suggest that they are proteins. Apart from the fact that no other type of molecule has the necessary ability for specific recognition of the substance to be carried, carrier-mediated transport mechanisms show features that are reminiscent of enzyme catalysis, i.e. they are pH dependent, can be competitively inhibited by structurally similar compounds and poisoned by other compounds. Moreover, they show a relationship to the concentration of transported material that is essentially similar to that of substrate concentration on enzyme activity. It appears therefore that passive carrier-mediated transport may be a catalysed permeability in which the equilibrium of the reaction is not affected although the rate of attainment of equilibrium is greatly enhanced while in the case of active transport, there is a modification of the diffusion equilibrium as a result of the coupling of the transport process to an energy-yielding reaction. 

Although the absorption of most drugs can be explained by passive diffusion, some compounds have specific transport mechanisms. An example is the absorption in the intestine of some penicillin derivatives, e.g. cyclacillin (1 aminocyclohexylpenicillin). This process is saturable, proceeds against an unfavourable concentration gradient and shows temperature dependence. Transport of amoxicillin is also carrier mediated but it is not an active process. Since these materials are xenobiotics, the transport mechanism is probably one which serves some other function in the body. The two penicillins probably share the same carrier since they are mutually competitive. Digitalis and other cardioselective glycosides also demonstrate behaviour not compatible with simple partition theory which suggests carrier-mediated transport. 

Substances can be transported across epithelial membranes by simple passive diffusion, carrier-mediated diffusion, and active transport, in addition to other specialized mechanisms, including endocytosis. 

Carrier-mediated passage of a molecular entity across a membrane (or other barrier). Facilitated transport follows saturation kinetics ie, the rate of transport at elevated concentrations of the transportable substrate reaches a maximum that reflects the concentration of carriers/transporters. In this respect, the kinetics resemble the Michaelis-Menten behavior of enzyme-catalyzed reactions. Facilitated diffusion systems are often stereo-specific, and they are subject to competitive inhibition. Facilitated transport systems are also distinguished from active transport systems which work against a concentration barrier and require a source of free energy. Simple diffusion often occurs in parallel to facilitated diffusion, and one must correct facilitated transport for the basal rate. This is usually evident when a plot of transport rate versus substrate concentration reaches a limiting nonzero rate at saturating substrate While the term passive transport has been used synonymously with facilitated transport, others have suggested that this term may be confused with or mistaken for simple diffusion. See Membrane Transport Kinetics... 

Passive diffusion of compounds into the tubules is proportional to the concentration in the bloodstream, so the greater the amount in the blood, the greater will be the rate of elimination. However, when excretion is mediated via active transport or facilitated diffusion, which involves the use of specific carriers, the rate of elimination is constant, and the carrier... 

The carrier-mediated active transport system of calcium is responsible for the relaxation of muscle. However, the rate of efflux from sarcoplasmic reticulum membranes during reversal of the transport process is 102 to 104 orders too low to account for the massive calcium release from sarcoplasmic reticulum in stimulated muscle. Instead, passive diffusion of calcium across the sarcoplasmic reticulum membrane will proceed during excitation of muscle178,179,186. The rate of calcium release observed during excitation is 1.000-3.000 p moles/mg protein/min which is an increase of about 104 to 10s over the resting state. 

The nasal epithelium possesses selective absorption characteristics similar to those of a semipermeable membrane, i.e., it allows a rapid passage of some compounds while preventing the passage of others. The process of transportation across the nasal mucosa involves either passive diffusion, via paracellular or transcellular mechanisms, or occurs via active processes mediated by membrane-bound carriers or membrane-derived vesicles involving endo- or transcytosis. 

Passive diffusion, carrier-mediated, or active transport across sinusoidal membrane... 

When a saturable transporter is involved in the permeation process, the permeability is no longer a constant value but is dependent on the concentration of the substrate. In that case it is necessary to characterize the parameters of the carrier-mediated process, Km, the Michaelis-Menten constant related with the affinity by the substrate and Vmax, the maximal velocity of transport. If a passive diffusion process occurs simultaneously to the active transport pathway then it is necessary to evaluate the contribution of each transport mechanism. An example of how to characterize the parameters in two experimental systems and how to correlate them are described in the next section. 

L-a-methyldopa a substrate for the amino acid transporter. In Caco-2 cells, the active transport of this dmg by the amino acid transporter was seven times higher than transport by passive diffusion. Its absorption may be further increased by upregulating the amino acid transporter, as has been observed in the 20-70% stimulation of carrier-mediated amino acid transport by treatment of 0.2 mg/kg growth hormone. 

---